Clinical relevance of heterozygosis for aceruloplasminemia

Author(s)

Borges, Marina Dorigatti ^[1] ; de Albuquerque, Dulcineia Martins ^[1] ; Lanaro, Carolina ^[1] ; Costa, Fernando Ferreira ^[1] ; Fertrin, Kleber Yotsumoto ^{[1, 2]}

Affiliation

^[1] Univ Estadual Campinas, UNICAMP, Hemoctr Campinas, Hematol & Hemotherapy Ctr, Campinas, SP - Brazil

^[2] Univ Washington, Sch Med, Div Hematol, 1959 NE Pacific St, Box 358081, Seattle, WA 98195 - USA

• Document type: Journal article
• Source: AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS; v. 180, n. 4, p. 266-271, JUN 2019.
• Web of Science Citations: 0

Abstract

Aceruloplasminemia is a rare form of brain iron overload of autosomal recessive inheritance that results from mutations in the CP gene, encoding the iron oxidase ceruloplasmin. Homozygous aceruloplasminemia causes progressive neurodegenerative disease, anemia, and diabetes, and is usually diagnosed late in life upon investigation of anemia, high ferritin, or movement disorders, but its heterozygous state is less characterized and believed to be silent. Here we report two heterozygotes for new mutations causing aceruloplasminemia from whom peripheral blood samples were collected for complete blood counts, iron studies, and genotyping by automated sequencing. We then performed a systematic review of preview reports of heterozygotes with data on genotype and clinical findings. Heterozygosity for aceruloplasminemia invariably causes reduced ceruloplasmin levels, and similarly to previews reports in the literature, our cases did not present with anemia. Mild hyperferritinemia was found only in two reports. Nevertheless, 5 out of 11 variants have been associated with significant neurological symptoms despite the presence of one wild-type alelle. This review contributes to better genetic counseling of heterozygotes for CP gene variants and supports that measuring ceruloplasmin levels may be useful when investigating patients with movement disorders or rare cases of unexplained high ferritin. (AU)

• FAPESP's process: 16/08072-9 - Characterization of molecular changes in patients with aceruloplasminemia
• Grantee: Marina Dorigatti Borges
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 14/00984-3 - Red blood cell disorders: pathophysiology and new therapeutic approaches
• Grantee: Fernando Ferreira Costa
• Support Opportunities: Research Projects - Thematic Grants